We herein describe a time-of-flight (TOF) technique to localize in 3D the position of a small fluorophore-filled
inclusion immersed in a scattering medium. To achieve this, we exploit the arrival time of early excited and
fluoresced photons. This is an embodiment of fluorescence diffuse optical tomography (FDOT) which aims to
find the position of fluorescent heterogeneities in 3D in thick turbid media non-invasively via optical imaging
techniques. In Ref. 4, we gave a short review of previous work on the problem of localizing a fluorescent
inclusion via time-resolved measurements. This will not be discussed again here.
In previous work, we have introduced a numerical constant fraction discrimination (NCFD) technique for processing
time-resolved optical signals. It allows to extract, in a stable manner, the arrival time of early photons
emitted by a fluorescent inclusion embedded in a scattering medium. We showed experimentally that these
arrival times correlate quasi-linearly with inclusion depth. We now exploit this arrival time vs depth relationship
for inferring the inclusion position by way of a time of flight algorithm. The algorithm uses the relative arrival
times measured at several detector positions around the scattering medium with respect to a reference detector
position. The latter is chosen as that detector position for which the arrival time is shortest. Our approach
provides accurate inclusion localization, showing the potential of direct time-of-flight fluorescence diffuse optical
tomography.
Recent advances in the design and fabrication of avalanche photodiodes (APDs) and quenching circuits for timecorrelated
single photon counting (TCSPC) have made available detectors with timing resolutions comparable
to microchannel plate photomultiplier tubes (MCP-PMTs). The latter, were until recently the best TCSPC
detectors in terms of temporal resolution (≤30ps). Comparable resolutions can now be obtained with TCSPC
APDs at a much lower cost. It should also be possible to manufacture APDs with standard electronics fabrication
processes in a near future. This will contribute to further decrease their price and ease their integration in
complex multi-channel detection systems, as required in diuse optical imaging (DOI) and tomography (DOT).
We present, to our knowledge for the first time, results which demonstrate that, despite their small sensitive area,
TCSPC APDs can be used in time-domain (TD) DOT and more generally in TD DOI. With appropriate optical
design of the detection channel, our experiments show that it is possible to obtain comparable measurements
with APDs as with PMTs.
We introduce a novel non-contact fluorescence diffuse optical tomography (FDOT) approach for localizing a
fluorescent inclusion embedded in a scattering medium. It uses the time of flight of early photons arriving at several detector positions around the medium. It is a true and direct time-of-flight approach in that arrival
times are converted to distance. The arrival time of early photons is found via a recently introduced numerical
constant fraction discriminator applied to fluoresced photons time-of-flight distributions (fluorescence time pointspread
functions (FTPSFs)). Time-correlated single photon counting and an ultrafast photon counting avalanche
photodiode are used for measuring FTPSFs that form tomographic data sets. The FDOT localization algorithm
proceeds in two steps. The first determines the angular position of the inclusion as the average, over projections, of
angular detector positions with smallest arrival time. The second determines the inclusion's radial position based
on relative arrival times obtained at several detector positions within each tomographic projection relatively to
a reference detector position, the latter being that of shortest arrival time in the projection. The radial position
found minimizes the discrepancy between relative arrival times computed for several possible inclusion positions
and relative arrival times deduced from experimental data. Two methods are presented for this.
The design and fabrication of time-correlated single photon counting (TCSPC) avalanche photodiodes (APDs)
and associated quenching circuits have made significant progresses in recent years. APDs with temporal resolutions
comparable to microchannel plate photomultiplier tubes (MCP-PMTs) are now available. MCP-PMTs
were until these progresses the best TCSPC detectors with timing resolutions down to 30ps. APDs can now
achieve these resolutions at a fraction of the cost. Work is under way to make the manufacturing of TCSPC
APDs compatible with standard electronics fabrication practices. This should allow to further reduce their cost
and render them easier to integrate in complex multi-channel TCSPC electronics, as needed in diffuse optical
tomography (DOT) systems. Even if their sensitive area is much smaller than that of the ubiquitous PMT
used in TCSPC, we show that with appropriate selection of optical components, TCSPC APDs can be used in
time-domain DOT. To support this, we present experimental data and calculations clearly demonstrating that
comparable measurements can be obtained with APDs and PMTs. We are, to our knowledge, the first group using APDs in TD DOT, in particular in non-contact TD fluorescence DOT.
We develop a novel approach to infer depth information about a small fluorophore-filled inclusion immersed in a scattering medium. It relies on time-resolved measurements of the time of flight distribution of emitted fluorescent photons after short pulse laser excitation. The approach uses a novel numerical constant fraction discrimination technique to assign a stable arrival time to the distribution's early photons. Our experimental results show a linear relationship between these arrival times and the position of the inclusion. This approach will serve as a useful technique in fluorescence diffuse optical tomography.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.